Overview of hyperviscosity syndromes

1. HYPERVISCOSITY SYNDROMES

2. Definition
Viscosity refers to resistance to flow or
stickiness, from a latin word “viscum alba”
Hyperviscosity syndromes (HVS) refers to
clinical sequelae of increased blood viscosity

3. CAUSES
 Elevated blood, plasma or serum viscosity occurs in number of hematological
conditions such as;
INCREASED IMMUNOGLOBULINS:
multiple myeloma
waldenstrom macroglobulinemia
connective tissue disease
INCREASED BLOOD CELLS: hyperproliferative states such as;
leukemias
polycythemias
thrombocytosis
myloproliferative disorders
REDUCED DEFORMABILITY OF RBCs:
spherocytosis
sickle cell disease
RHEUMATOID HVS is rare but can occur due to aggregates of RF or intermediate IgG
complexes

4. PATHOPHYSIOLOGY
 As serum proteins or cellular components increases, the blood become
more viscous. It leads to vascular stasis and tissue hypoperfusion then
lead to signs and symptoms of HVS syndromes.
 confusion and mental status changes results from the increased viscosity
of the blood and decreased cerebral blood flow.
 This sludging leads to segmental dilatation of retinal veins and retinal
hemorrhages.
 mucosal bleed may occur from prolonged bleeding time caused by
myeloma proteins interfering with platelets functions.
 cardiopulmonary symptoms also result from sludging of blood and
decreased microvascular circulation.

5. SIGNS AND SYMPTOMS
 The triad of mucosal bleeding, visual disturbances and
neurological symptoms.
 Tendency to bleed; most common manifestation. Gum
bleeding, epistaxis, PR bleed, menorrhagia and persistant
bleeding from minor procedures.
 Cardiopulmonary symptoms: such as SOB, hypotension,
respiratory failure
 visual changes ranging from blurring to vision loss
 Neurological menifestations such as: vertigo, tinnitus,
hearing loss, paresthesias, ataxia, headaches, seizures,
somnolence progressing to stupor and coma.

6.  Dermatological manifestations such as Raynaud
phenomenon, palpable purpura, digital infarcts, peripheral
gangrene
 renal manifestations such as hematuria, sterile pyuria,
nephrotic or nephritic syndromes
 Constitutional symptoms such as fatigue, weakness,
anorexia

8. The clinician should have a high level of suspicion
for hyperviscosity syndromes in patients with
unexplained coma, altered mental status or
unexplained shortness of breath especially, in
patients with an underlying hematologic disorders.

9. PHYSICAL FINDINGS
 Bruises on the skin
 Facial flushing
 Blood blisters in the mouth or back af the eye.
 Decrease GCS, ataxia, nystagmus
 Signs of CHF
 Splenomegaly, palpable lymph nodes
 Opthalmic examination may reveal:
decreased visual acuity
dilated retinal veins
sausage-linked or boxer segmentation of retinal veins
retinal hemorrhages

10. Clinical sequelae of HVS
 CHF
 Ischemic acute tubular necrosis
 Pulmonary edema
 Multiorgan failure

11. DIAGNOSIS
 History and clinical examination:
any patient presented with unexplained coma/ altered
sensorium, SOB, and visual changes.
any patient present with classical triad of mucosal bleed,
visual changes and neurological manifestations and especially
those with underlying blood disorders.
 Lab investigations
 imaging studies

12. Lab clues:
 CBC: erythrocytosis, leukemias, thrombocytosis, normocytic
normochromic anemia
 Globulin gap more than 4
 Metabolic panel: deranged RFTs, hypercalcemia,
pseudohyponatremia
 Urine analysis: proteinuria, sterile pyuria, BENCE JONES
PROTEINS.
 Protein electrophoresis
 coagulation profile
 Important markers such as LDH, VIT B12, B2 microglobulins,
ALP, uric acid

13. Imaging studies
 Bone scan
 CXR
 Ultrasound abdomen and pelvis
 CT & MRI brain
 Echocardiography

14. DIAGNOSIS
 The diagnosis of HVS is confirmed by measurement of
elevated serum viscosity in patients with characteristic clinical
manifestations of HVS. But there are no exact cut-off exists for
serum viscosity.
 Normal serum viscosity: 1.4-1.8 units centipoises
 Symptoms usually not seen at viscosities less than 4.
 HVS usually manifests when viscosity is more than 5 units.

15. Measuring viscosity
 Classically measured in one of 2 ways;
 1: by determining rate of fluid flow as a result of applying a predefined
force
 2: by measuring the amount of force required to achieve a predefined rate
of fluid flow.
 Approximately 75% of labs use a “capillary tube” also known as
“Ostwald tube” viscometer to measure viscosity.

17. Treatment
Hydration therapy
 early apheresis such as plasmapheresis , leukaphresis,
platletphresis
 phlebotomy
Standard therapies for bleeding, CHF
 be caution with blood transfusions even when needed
Diuretics may even worse the condition

18. Plasmapheresis
 Treatment of choice in most cases for initial management
and stabilization
 plasmapheresis demonstrated to reverse the retinopathy and
other manifestations of HVS in most patients
 As bleeding is a most common manifestation, urgent
plasmapheresis using a cell separator should be used to
reduced the likelihood of blindness from retinal hemorrhage/
retinal detachment.
 Plasma exchange reduces the plasma viscosity by 20%-30%
per session

19. Plasmapheresis

20. Treatment algorithm
for hyperviscosity
syndrome in WM. (a)
Bendamustine/rituxim
ab. (b)
Dexamethasone/cycl
ophosphamide/rituxi
mab. (c)
Bortezomib/dexamet
hasone/rituximab.

21. Prognosis
Definitive treatment of HVS depend upon the
underlying condition
If the underlying disorder kept untreated the HVS will
recur again
Prognosis of HVS depend upon underlying condition,
its severity and its response to treatment.